product name Letrozole
Description: Letrozole, also known as CGS-20267, is a third generation, nonsteroidal inhibitor of aromatase with IC50 of 0.07-20 nM in cell-free assays. As a third-generation aromatase inhibitor, letrozole inhibits aromatase selectively and reversibly, which may result in growth inhibition of estrogen-dependent breast cancer cells. Letrozole administration can reduce spine synapse and axon outgrowth and it also will decrease the expression of estrogen receptor (ER). Letrozole is proved to promote FSH release from the hypothalamic pituitary axis by responding to decreased estrogen (E) feedback.
References: J Steroid Biochem Mol Biol. 2003 Oct;87(1):35-45; J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):1021-7.
285.3
Formula
C17H11N5
CAS No.
112809-51-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 57 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% CMC: 10 mg/mL
Synonyms
CGS 20267
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393268
| In Vitro |
In vitro activity: Letrozole potently inhibits aromatase derived from a variety of different sources including human placental microsomes, particulate fractions of human breast cancer, rat ovarian microsomes, MCF-7 cells transfected with aromatase (MCF-7Ca), JEG-3 human choriocarcinoma cells , CHO cells, hamster ovarian tissue, and particulate fractions of human breast cancer with IC50 of 11, 2, 7, 0.07, 0.07, 1.4, 20 and 0.8 nM. In the non-cellular systems, the IC50 of letrozole is calculated to be 1-13 nM. Letrozole maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 μM with an IC50 of 0.02 μM and does not significantly affect progesterone production up to 350 μM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production is inhibited by with an IC50 of 210 μM. Letrozole inhibits growth of the MCF-7 epithelial breast cancer cells in a dose-dependent way with IC50 of 1 nM. Inhibition can be observesed even at the very low concentrations tested (0.1 nM). Treatment of normal MCF-12A epithelial cells with letrozole did not affect their growth even when high letrozole concentrations (100 nM) or prolonged culture times. Letrozole (10 nM) significantly suppressed the stimulatory effects of 4-androstene-3,17-dione (100 nM) or testosterone (100 nM) on MCF-7 cell proliferation. Concurrent administration of 17-β-estradiol with letrozole (10 nM) decreased the stimulatory effect of the enzymatic activity of MMP-2 and – 9 released by estradiol. Kinase Assay: The assay is performed in a total volume of 1 mL at 37 ℃. Unless otherwise noted, the incubation mixture contains 11 nM [4- 14C] androstene-3, 17-dione ([4- 14C]A), 24 mM NADPH (tetrasodium salt Type III), the appropriate concentrations of the desired inhibitor, and 120 μg of microsomal protein. The (4- 14C)A is added as a solution in 1.7% ethanol in 0.05 M potassium phosphate buffer (pH 7.4), so that the final concentration of ethanol does not exceed 0.02% (v/v). The reaction is started by the addition of enzyme and stopped after 20 min by the addition of 7 vol of ethyl acetate. The mixture is agitated on a vortex mixer and centrifuged at 600 g for 5 min. The aqueous phase is re-extracted with 7 vol of ethyl acetate, and the combined extracts are evaporated to dryness using an Evapo-Mix. Over 99% of the radio- active of [4- 14C] added is recovered using this extraction system. The residue obtained is dissolved in 150 μL acetone, and 100 μL aliquots are chromatographed for 65 min on thin-layer plates precoated with silica gel 60 using ethyl: acetate: isooctane (140:60, v/v; system A) or toluene: chloroform: methanol (70:140:20; system B). The radioactive zones of the plate are located with a Berthold LB 2760 thin-layer scanner. The radioactive estradiol (E2) and estrone (E1) neaks are identified by comparison with authentic standards. The corresponding bonding band of silica gel is transferred to vials containing 10 mL of scintillation fluid, and counted with a 6880 Liquid Scintillation system. Cell Assay: Cells (Human breast cancer cells MCF-7) are seeded in duplicate at 5,000 to 10,000 cells per well in 24-well plates. The day after plating, different concentrations of Letrozole are added. At the end of incubation, cells are trypsinizated and placed in Isotone solution and counted immediately using a Coulter particle-counter. |
|---|---|
| In Vivo | Letrozole inhibits aromatase in vivo with ED50 of 1-3 μg/kg p.o. Letrozole displays anti-endocrine effects. Letrozole inhibits androstenedione-induced uterine hypertrophy in immature rats with ED50 of 1-3 μg/kg. In the adult female rat, Letrozole (0.3-1 mg/kg daily p.o., 14 days) completely interrupts ovarian cyclicity and reduces uterine weight and serum estradiol (E2) concentrations to a similar extent to that seen after ovariectomy. Letrozole induces dose-dependent regression of estrogen-dependent, 9,10-dimethylbenz-a-anthracene (DMBA)-induced mammary tumors in adult female rats. The ED50 for Letrozole is determined to be 10 – 30 µg/kg/day, with complete inhibition at a daily dose of 10 µg/day. Letrozole produces dose-dependent inhibition of tumor growth of MCF-7 cells transfected with human aromatase gene (MCF-7Ca) implanted athymic nude mice, with complete inhibition at 20 mg/kg per day p.o. |
| Animal model | Human breast carcinoma xenografts MCF-7 with human aromatase gene (MCF-7Ca) |
| Formulation & Dosage | Formulated in 0.5% (w/v) solution of carboxymethylcellulos; 20 mg/kg/day; oral gavage |
| References | J Steroid Biochem Mol Biol. 2003 Oct;87(1):35-45; J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):1021-7. |
Related Posts
product name Letrozole
Description: Letrozole, also known as CGS-20267, is a third generation, nonsteroidal inhibitor of aromatase with IC50 of 0.07-20 nM in cell-free assays. As a third-generation aromatase inhibitor, letrozole inhibits aromatase selectively and reversibly, which may result in growth inhibition of estrogen-dependent breast cancer cells. Letrozole administration can reduce spine synapse and axon outgrowth and it also will decrease the expression of estrogen receptor (ER). Letrozole is proved to promote FSH release from the hypothalamic pituitary axis by responding to decreased estrogen (E) feedback.
References: J Steroid Biochem Mol Biol. 2003 Oct;87(1):35-45; J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):1021-7.
285.3
Formula
C17H11N5
CAS No.
112809-51-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 57 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% CMC: 10 mg/mL
Synonyms
CGS 20267
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393268
| In Vitro |
In vitro activity: Letrozole potently inhibits aromatase derived from a variety of different sources including human placental microsomes, particulate fractions of human breast cancer, rat ovarian microsomes, MCF-7 cells transfected with aromatase (MCF-7Ca), JEG-3 human choriocarcinoma cells , CHO cells, hamster ovarian tissue, and particulate fractions of human breast cancer with IC50 of 11, 2, 7, 0.07, 0.07, 1.4, 20 and 0.8 nM. In the non-cellular systems, the IC50 of letrozole is calculated to be 1-13 nM. Letrozole maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 μM with an IC50 of 0.02 μM and does not significantly affect progesterone production up to 350 μM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production is inhibited by with an IC50 of 210 μM. Letrozole inhibits growth of the MCF-7 epithelial breast cancer cells in a dose-dependent way with IC50 of 1 nM. Inhibition can be observesed even at the very low concentrations tested (0.1 nM). Treatment of normal MCF-12A epithelial cells with letrozole did not affect their growth even when high letrozole concentrations (100 nM) or prolonged culture times. Letrozole (10 nM) significantly suppressed the stimulatory effects of 4-androstene-3,17-dione (100 nM) or testosterone (100 nM) on MCF-7 cell proliferation. Concurrent administration of 17-β-estradiol with letrozole (10 nM) decreased the stimulatory effect of the enzymatic activity of MMP-2 and – 9 released by estradiol. Kinase Assay: The assay is performed in a total volume of 1 mL at 37 ℃. Unless otherwise noted, the incubation mixture contains 11 nM [4- 14C] androstene-3, 17-dione ([4- 14C]A), 24 mM NADPH (tetrasodium salt Type III), the appropriate concentrations of the desired inhibitor, and 120 μg of microsomal protein. The (4- 14C)A is added as a solution in 1.7% ethanol in 0.05 M potassium phosphate buffer (pH 7.4), so that the final concentration of ethanol does not exceed 0.02% (v/v). The reaction is started by the addition of enzyme and stopped after 20 min by the addition of 7 vol of ethyl acetate. The mixture is agitated on a vortex mixer and centrifuged at 600 g for 5 min. The aqueous phase is re-extracted with 7 vol of ethyl acetate, and the combined extracts are evaporated to dryness using an Evapo-Mix. Over 99% of the radio- active of [4- 14C] added is recovered using this extraction system. The residue obtained is dissolved in 150 μL acetone, and 100 μL aliquots are chromatographed for 65 min on thin-layer plates precoated with silica gel 60 using ethyl: acetate: isooctane (140:60, v/v; system A) or toluene: chloroform: methanol (70:140:20; system B). The radioactive zones of the plate are located with a Berthold LB 2760 thin-layer scanner. The radioactive estradiol (E2) and estrone (E1) neaks are identified by comparison with authentic standards. The corresponding bonding band of silica gel is transferred to vials containing 10 mL of scintillation fluid, and counted with a 6880 Liquid Scintillation system. Cell Assay: Cells (Human breast cancer cells MCF-7) are seeded in duplicate at 5,000 to 10,000 cells per well in 24-well plates. The day after plating, different concentrations of Letrozole are added. At the end of incubation, cells are trypsinizated and placed in Isotone solution and counted immediately using a Coulter particle-counter. |
|---|---|
| In Vivo | Letrozole inhibits aromatase in vivo with ED50 of 1-3 μg/kg p.o. Letrozole displays anti-endocrine effects. Letrozole inhibits androstenedione-induced uterine hypertrophy in immature rats with ED50 of 1-3 μg/kg. In the adult female rat, Letrozole (0.3-1 mg/kg daily p.o., 14 days) completely interrupts ovarian cyclicity and reduces uterine weight and serum estradiol (E2) concentrations to a similar extent to that seen after ovariectomy. Letrozole induces dose-dependent regression of estrogen-dependent, 9,10-dimethylbenz-a-anthracene (DMBA)-induced mammary tumors in adult female rats. The ED50 for Letrozole is determined to be 10 – 30 µg/kg/day, with complete inhibition at a daily dose of 10 µg/day. Letrozole produces dose-dependent inhibition of tumor growth of MCF-7 cells transfected with human aromatase gene (MCF-7Ca) implanted athymic nude mice, with complete inhibition at 20 mg/kg per day p.o. |
| Animal model | Human breast carcinoma xenografts MCF-7 with human aromatase gene (MCF-7Ca) |
| Formulation & Dosage | Formulated in 0.5% (w/v) solution of carboxymethylcellulos; 20 mg/kg/day; oral gavage |
| References | J Steroid Biochem Mol Biol. 2003 Oct;87(1):35-45; J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):1021-7. |